Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metabolomics approaches are powerful tools in systematic study of overall metabolic changes in response to disease or interventions. In this study, mass spectrometry-based metabolomics studies were performed to investigate the regulatory effect of moderate intensity of exercise on db/db diabetic mice in skeletal muscle. Both liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have been carried out to monitor a wide range of regulated metabolites. Ninety-five metabolites were identified which contributing to the discrimination of db/m + control and db/db diabetic mice. The regulatory effects of exercise on these metabolites were mainly focusing on attenuating the levels of long-chain fatty acids (C14 to C18) and medium-to long-chain acylcarnitines (C12 to C18), indicated that exercise might play a positive role in inhibiting the accumulation of excessive lipids, which is positively related to insulin resistance. In addition, uric acid, which is a risk factor for inflammation, cardiovascular complications, and fatty liver in diabetic patients, together with its intermediates (such as inosinic acid, hypoxanthine, etc.) in purine metabolism pathway, were also substantially down regulated after exercise, indicating exercise might also be protective against hyperuricemia related risks in T2DM. These findings reveal that moderate intensity of exercise might play a positive role in improving the efficiency of lipid metabolism in skeletal muscle and meanwhile enhancing uric acid clearance to prevent lipid accumulation, which might contribute to improved body fitness and body muscle composition.

Keywords: Db/db; Diabetes; Exercise; Mass spectrometry; Metabolomics; Skeletal muscle.